Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic, and it is the most common cause of liver diseases. The patients with severe insulin-resistant diabetes having high body mass index (BMI), high-grade adipose tissue insulin resistance, and high hepatocellular triacylglycerols (triglycerides; TAG) content develop hepatic fibrosis within a 5-year follow-up. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol (DAG), fatty acyl CoA, or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/nonalcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with an increase in saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in the liver tissue of patients with NASH. Hepatocyte lipoapoptosis is a critical feature of NASH. In the "second hit," reduced glutathione levels due to oxidative stress lead to the overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused at least by two ineffectual cyclical pathways. First is the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and the second is the Kelch like-ECH-associated protein 1 (Keap1)-nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. In clinical practice, on ultrasonographic examination, the elevation of transaminases, γ-glutamyltransferase, and the aspartate transaminase to platelet ratio index indicates NAFLD. Fibrosis-4 index, NAFLD fibrosis score, and cytokeratin18 are used for grading steatosis, staging fibrosis, and discriminating the NASH from simple steatosis, respectively. In addition to ultrasonography, "controlled attenuation parameter," "magnetic resonance imaging proton-density fat fraction," "ultrasound-based elastography," "magnetic resonance elastography," "acoustic radiation force impulse elastography imaging," "two-dimensional shear-wave elastography with supersonic imagine," and "vibration-controlled transient elastography" are recommended as combined tests with serum markers in the clinical evaluation of NAFLD. However, to confirm the diagnosis of NAFLD, a liver biopsy is the gold standard. Insulin resistance-associated hyperinsulinemia directly accelerates fibrogenesis during NAFLD development. Although hepatocyte lipoapoptosis is a key driving force of fibrosis progression, hepatic stellate cells and extracellular matrix cells are major fibrogenic effectors. Thereby, these are pharmacological targets of therapies in developing hepatic fibrosis. Nonpharmacological management of NAFLD mainly consists of two alternatives: lifestyle modification and metabolic surgery. Many pharmacological agents that are thought to be effective in the treatment of NAFLD have been tried, but due to lack of ability to attenuate NAFLD, or adverse effects during the phase trials, the vast majority could not be licensed.

Elucidating the role of hepatic enzymes in spontaneous abortion: a Mendelian randomization approach.

Background: While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA. Methods: Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis. Results: The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899). Conclusion: The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA.

Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India.

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes.

Seroepidemiology of hepatitis B virus (HBV) and relationship to serum transaminase levels in Indian population.

Background: Hepatitis B virus (HBV) infection is a serious public health issue that must be addressed. Aim: The goal of this study was to investigate the correlation between serological status for hepatitis Be antigen (HBeAg)/anti-HBe, serum transaminase levels, and serum HBV-DNA in patients with chronic HBV infection. Methods: A retrospective observational study with 620 patients with persistent HBV infection (mean age, 36.35 years; 506 men) was conducted. All patients tested positive for hepatitis B surface antigen (HBsAg). Liver profile, HBeAg, and anti-HBe antibody tests were conducted for all patients. Additionally, serum HBV DNA was examined using a DNA assay in these individuals. Results: Of 620 patients, 114 (18.39%) were HBeAg-positive and 506 (81.61%) HBeAg-negative. A detectable level of HBV DNA was found in 89.79% of HBeAg-positive/anti-HBe negative patients compared to HBeAg-negative/anti-HBe positive carriers 33.69% (P value <0.0001). The median viral load was significantly higher in HBeAg-positive cases (4.72 log10 copies/mL) than in HBeAg-negative individuals (4.23 log10 copies/mL; P = 0.997). Additionally, a higher proportion of HBeAg-positive samples (P = 0.0001) had HBV-DNA levels above 10,000 copies/mL.

Prevalence and Associated Factors of Liver Enzyme Abnormalities Among Bangladeshi Women: A Cross-Sectional Study.

Background Liver enzyme abnormalities can indicate underlying liver health issues and are influenced by various factors. This study aimed to investigate the prevalence of liver enzyme abnormalities and their associated factors among nonpregnant and nonlactating (NPNL) women in Bangladesh. Methodology A cross-sectional study was conducted among 251 NPNL Bangladeshi women. Data on demographic, socioeconomic, and health-related variables were collected. Logistic regression analysis was used to determine the association between liver enzyme abnormalities and associated factors. Results The prevalence of liver enzyme abnormalities among participants was determined, with associated factors such as age, body mass index (BMI), monthly income, and food security status examined. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in 54 (21.5%) and 47 (18.7%) of participants, respectively, with 116 (46.2%) exhibiting an AST/ALT ratio exceeding 1.00. Food insecurity was significantly associated with a higher prevalence of elevated ALT levels (24.4% vs. 8.7%, P = 0.02), as well as low monthly income (18.8%, 14.7% vs. 36.7%, P < 0.01) and higher BMI (11% vs. 27.7% and 25.6%, P = 0.02). Similar trends were observed for AST levels. Moreover, participants with a higher BMI exhibited significantly higher rates of at least one abnormal liver function enzyme (15.9% vs. 34.9%, P = 0.01). Logistic regression analysis revealed a significant association between abnormal liver enzyme levels and certain demographic and socioeconomic factors, specifically BMI and age. Conclusions This study provides insights into the prevalence of liver enzyme abnormalities and their associated factors among NPNL Bangladeshi women. The findings underscore the importance of addressing factors such as BMI and age in mitigating liver health issues in this population. Further research and targeted interventions are warranted to address these concerns effectively.

On a deterministic mathematical model which efficiently predicts the protective effect of a plant extract mixture in cirrhotic rats.

In this work, we propose a mathematical model that describes liver evolution and concentrations of alanine aminotransferase and aspartate aminotransferase in a group of rats damaged with carbon tetrachloride. Carbon tetrachloride was employed to induce cirrhosis. A second groups damaged with carbon tetrachloride was exposed simultaneously a plant extract as hepatoprotective agent. The model reproduces the data obtained in the experiment reported in [Rev. Cub. Plant. Med. 22(1), 2017], and predicts that using the plants extract helps to get a better natural recovery after the treatment. Computer simulations show that the extract reduces the damage velocity but does not avoid it entirely. The present paper is the first report in the literature in which a mathematical model reliably predicts the protective effect of a plant extract mixture in rats with cirrhosis disease. The results reported in this manuscript could be used in the future to help in fighting cirrhotic conditions in humans, though more experimental and mathematical work is required in that case.

The Comparison of the Anti-inflammatory Efficacy of Phytochemical Extracts in Punica granatum and Lawsonia inermis Among Patients Diagnosed With Chronic Periodontitis.

Introduction The oral cavity is the gateway to the human body. Periodontitis is a common inflammatory condition affecting the oral cavity and a known etiological cause of tissue destruction, discomfort, and halitosis. Pomegranate (Punica granatum) and henna (Lawsonia inermis) are herbs known to mankind from time immemorial whose extracts are proven to fight inflammation. The current study was done to evaluate the phytochemical anti-inflammatory efficacy of Punica and Lawsonia in patients with chronic periodontitis and test the potency of herbal mouthwashes in fighting the inflammatory condition affecting the oral cavity using distilled water as a control group. Materials and methods A double-blinded randomized control trial was conducted on 60 patients who were recruited and divided into three groups, in which 20 patients were prescribed with pomegranate (Punica: n=20) mouthwash and 20 patients with henna (Lawsonia: n=20) mouthwash along with distilled water (n=20). All patients were randomly allocated using the coin toss method and advised to use the prescribed mouthwash for a period of two weeks. Unstimulated saliva was collected before using the mouthwash, and salivary enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) and their levels were assessed spectrometrically using the infrared spectrophotoscopy (IFSC) method. Each patient was assigned a mouthwash and recalled after two weeks. Unstimulated saliva was again collected, and salivary activity levels of enzymes AST, ALT, and LDH were analyzed after using mouthwash in a similar method as done before. Later on, the salivary levels of enzymes AST, ALT, and LDH were compared before and after the usage of mouthwashes. Statistical significance was seen in the salivary enzymatic activity of AST, ALT, and LDH before and after using Punica and Lawsonia mouthwashes due to their potent phytochemical action in fighting inflammation. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 22 (IBM SPSS Statistics, Armonk, NY). The Shapiro-Wilk test was used to determine the normality and significance; intragroup comparison was done using the Wilcoxon signed-rank test and Mann-Whitney U test. Intergroup comparison was done using the Kruskal-Wallis test. Results Punica patients had much lower levels of salivary AST and ALT (p<0.001) and a decrease in LDH (p=0.002) after the usage of mouthwash for a period of two weeks. Also, patients using Lawsonia as herbal mouthwash had reduction in the values of AST (p=0.001) and LDH (p=0.003) and prominent reduction in ALT (p<0.001) after a period of two weeks. But in the case of patients using distilled water, there was an increase in the salivary enzymatic activity of AST and ALT, which was statistically significant (p<0.001), and LDH (p=0.006) depicting the disease progression even after using mouthwash for the given time period of two weeks. Conclusion This study demonstrated that both Punica and Lawsonia were effective in reducing the inflammation in patients diagnosed with chronic periodontitis. However, when intergroup comparison was done, the anti-inflammatory efficacy was superior in Punica with significant reduction in the parameters such as of AST, ALT, and LDH when compared to Lawsonia owing to its potent phytochemical constituency in cutting down the inflammation. Hence, Punica can be used as an implicated effective anti-inflammatory herbal mouthwash.

Low-Cost Point-of-Care Monitoring of ALT and AST Is Promising for Faster Decision Making and Diagnosis of Acute Liver Injury.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are important liver enzymes in clinical settings. Their levels are known to be elevated in individuals with underlying liver diseases and those consuming hepatotoxic drugs. Serum ALT and AST levels are crucial for diagnosing and assessing liver diseases. Serum ALT is considered the most reliable and specific candidate as a disease biomarker for liver diseases. ALT and AST levels are routinely analyzed in high-risk individuals for the bioanalysis of both liver function and complications associated with drug-induced liver injury. Typically, ALT and AST require blood sampling, serum separation, and testing. Traditional methods require expensive or sophisticated equipment and trained specialists, which is often time-consuming. Therefore, developing countries have limited or no access to these methods. To address the above issues, we hypothesize that low-cost biosensing methods (paper-based assays) can be applied to the analysis of ALT and AST levels in biological fluids. The paper-based biodetection technique can semi-quantitatively measure ALT and AST from capillary finger sticks, and it will pave the way for the development of an inexpensive and rapid alternative method for the early detection and diagnosis of liver diseases. This method is expected to significantly reduce the economic burden and aid routine clinical analysis in both developed and underdeveloped countries. The development of low-cost testing platforms and their diagnostic utility will be extremely beneficial in helping millions of patients with liver disorders.

The Impact of Liver Chemistries on Respiratory Failure among Hemodialysis Patients with COVID-19 during the Omicron Wave.

Objective Although the coronavirus disease 2019 (COVID-19) Omicron variant causes less severe symptoms than previous variants, early indicators for respiratory failure are needed in hemodialysis patients, who have a higher mortality rate than the general population. Liver chemistries are known to reflect the severity of COVID-19 in the general population. This study explored the early indicators for worsened respiratory failure based on patient characteristics, including liver chemistries. Methods This retrospective study included 117 patients admitted for COVID-19 during the Omicron wave. Respiratory failure was defined as oxygen requirement during treatment. Information on the symptoms and clinical characteristics, including liver chemistries [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], at admission was collected. Results Thirty-five patients (29.9%) required oxygen supply during treatment. In the multivariate logistic regression analyses, AST [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=0.029], ALT (OR 1.09, 95% CI 1.02-1.18, p=0.009), and moderate COVID-19 illness (Model including AST, OR 6.95, 95% CI 2.23-23.17, p<0.001; Model including ALT, OR 7.19, 95% CI 2.21-25.22, p=0.001) were independent predictors for respiratory failure. Based on the cutoff values determined by the receiver operating characteristic curve, higher AST (≥23 IU/L) and ALT levels (≥14 IU/L) were also independently associated with respiratory failure (higher AST: 64.3% vs. 18.8%, OR 3.44, 95% CI 1.08-11.10, p=0.035; higher ALT: 48.8% vs. 19.7%, OR 4.23, 95% CI 1.34-14.52, p=0.013, respectively). Conclusion The measurement of AST and ALT levels at baseline may help predict oxygen requirement in hemodialysis patients with COVID-19.

Advanced Stage Hepatic Fibrosis With Normal Liver Chemistries: A Case Report.

This is a case report on a patient with biopsy-proven stage 2 hepatic fibrosis who routinely has had normal liver chemistries. This is important because liver chemistry tests are the standard physicians use to assess general liver health. There is not an abundance of research on patients with advanced hepatic fibrosis who have normal liver chemistries, but the research that is available all agree that liver biopsy is the better way to get a clear picture of the disease state of the liver. Biopsies of the liver are not as easily accessible or as cost-effective as simple blood work though. Patients are also less likely to agree to undergo a procedure than to get blood drawn. These are all obstacles in regard to changing the standard in determining liver health from laboratory work to liver biopsies, in addition to liver chemistries. This case report aids in the research already available on how normal liver chemistries should not automatically rule out hepatic fibrosis. This patient proves that fibrosis can be happening, and the blood tests are not reflecting that change. Due to this, further research and investigation on liver fibrosis and normal liver chemistries should be done.

Aptasensors Are Conjectured as Promising ALT and AST Diagnostic Tools for the Early Diagnosis of Acute Liver Injury.

Abnormal levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in human serum are the most sensitive indicator of hepatocellular damage. Because liver-related health problems are directly linked to elevated levels of ALT and AST, it is important to develop accurate and rapid methods to detect these enzymes for the early diagnosis of liver disease and prevention of long-term liver damage. Several analytical methods have been developed for the detection of ALT and AST. However, these methods are based on complex mechanisms and require bulky instruments and laboratories, making them unsuitable for point-of-care application or in-house testing. Lateral flow assay (LFA)-based biosensors, on the other hand, provide rapid, accurate, and reliable results, are easy to operate, and are affordable for low-income populations. However, due to the storage, stability, batch-to-batch variations, and error margins, antibody-based LFAs are considered unaffordable for field applications. In this hypothesis, we propose the selection of aptamers with high affinity and specificity for the liver biomarkers ALT and AST to build an efficient LFA device for point-of-care applications. Though the aptamer-based LFA would be semiquantitative for ALT and AST, it would be an inexpensive option for the early detection and diagnosis of liver disease. Aptamer-based LFA is anticipated to minimize the economic burden. It can also be used for routine liver function tests regardless of the economic situation in each country. By developing a low-cost testing platform, millions of patients suffering from liver disease can be saved.

Mitigating Apoptotic and Inflammatory Signaling via Global Caspase Inhibition in Hibernating Ground Squirrels, Spermophilus lateralis.

AbstractIn most systems, the caspase cascade is activated during cellular stress and results in inflammation and apoptosis. Hibernators experience stressors such as extremely low body temperatures, bradycardia, possible ischemia and reperfusion, and acidosis. However, widespread inflammation and apoptosis would represent an energetic expense that is incompatible with hibernation. To better understand global caspase regulation during hibernation, we employed a systems-level approach and analyzed 11 caspases in ground squirrel liver that are involved in inflammatory (caspases 1, 4, 5, 11, and 12) and apoptotic (caspases 2, 6, 7, 8, 9, and 10) pathways. Western blots revealed liberation of active forms for two inflammatory (caspases 11 and 12) and two apoptotic (caspases 6 and 9) caspases during hibernation (e.g., p15, the most active fragment of caspase 6, increased 8.26±0.70-fold in interbout-aroused animals). We used specific peptide substrates to interrogate the four seemingly activated caspases and demonstrated no expected increases in proteolytic activity. Specific targets of these four caspases were similarly not cleaved, demonstrating that initiation of caspase activation may occur without concomitant downstream effects. Similarly, we found no evidence for upstream activation for caspase 9 signaling based on permeabilization of the outer mitochondrial membrane. We contend that these caspases are suppressed after seeming activation during hibernation. Incomplete caspase signaling is effectively mitigating the induction of widespread inflammation and apoptosis during hibernation.

Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials.

RATIONALE & OBJECTIVE: Tolvaptan is associated with risk of drug-induced liver injury when used to treat autosomal dominant polycystic kidney disease (ADPKD). After this risk was described based on the clinical trials TEMPO 3:4 and TEMPO 4:4, additional data from the REPRISE trial and a long-term extension of TEMPO 4:4, REPRISE, and other tolvaptan trials in ADPKD have become available. To further characterize the hepatic safety profile of tolvaptan, an analysis of the expanded dataset was conducted. STUDY DESIGN: Analysis of safety data from prospective clinical trials of tolvaptan. SETTING & PARTICIPANTS: Multicenter clinical trials including more than 2,900 tolvaptan-treated participants, more than 2,300 with at least 18 months of drug exposure. INTERVENTION: Tolvaptan administered twice daily in split-dose regimens. OUTCOMES: Frequency of liver enzyme level increases detected by regular laboratory monitoring. RESULTS: In the placebo-controlled REPRISE trial, more tolvaptan- than placebo-treated participants (38 of 681 [5.6%] vs 8 of 685 [1.2%]) experienced alanine aminotransferase level increases to >3× the upper limit of normal (ULN), similar to TEMPO 3:4 (40 of 957 [4.4%] vs 5 of 484 [1.0%]). No participant in REPRISE or the long-term extension experienced concurrent alanine aminotransferase level increases to >3× ULN and total bilirubin increases to >2× ULN ("Hy's Law" laboratory criteria). Based on the expanded dataset, liver enzyme increases most often occurred within 18 months after tolvaptan initiation and were less frequent thereafter. Increased levels returned to normal or near normal after treatment interruption or discontinuation. Thirty-eight patients were rechallenged with tolvaptan after the initial drug-induced liver injury episode, with return of liver enzyme level increases in 30; 1 additional participant showed a clinical "adaptation" after the initial episode, with resolution of the enzyme level increases despite continuation of tolvaptan. LIMITATIONS: Retrospective analysis. CONCLUSIONS: The absence of Hy's Law cases in REPRISE and the long-term extension trial support monthly liver enzyme monitoring during the first 18 months of tolvaptan exposure and every 3 months thereafter to detect and manage enzyme level increases, as is recommended on the drug label. FUNDING: Otsuka Pharmaceutical Development & Commercialization, Inc. TRIAL REGISTRATION: Trials included in the dataset were registered at ClinicalTrials.gov with study numbers NCT00428948 (TEMPO 3:4), NCT01214421 (TEMPO 4:4), NCT02160145 (REPRISE), and NCT02251275 (long-term extension).

Evaluation of Liver Enzymes in Normal Pregnancies in a University Hospital of Zabol Iran: A Cross-Sectional Study.

Objective: Changes in endocrine, nervous, renal, cardiovascular, and respiratory systems during pregnancy have been studied, but changes in liver function have been poorly studied. Therefore, the purpose of this study was to investigate the trend of changes in liver enzymes in normal pregnancy. Materials and methods: This prospective longitudinal study included 68 pregnant women who were referred to the Obstetrics and Gynecology Clinic of Amiral Momenin Hospital in Zabol in 2021. In terms of the trimester of pregnancy, the presence of underlying diseases, history of previous pregnancies, disorders of the enzymes of recent patients, the patients were evaluated, and the information from the patients' files was analyzed. Results: The average AST levels in pregnant women in the first, second, and third trimesters were 16.82, 17.47, and 18.00, respectively, which show that garlic consumption is increasing. The average PT in pregnant women decreased in the first, second, and third trimesters. The average direct and total bilirubin levels in pregnant women in the first and second trimesters showed a constant trend. The amount of total protein increased in pregnant women during the first, second, and third trimesters. In the second and third trimesters, the enzyme level was significantly higher in pregnant women than in nonpregnant women. The level of GGT in pregnant women in the first, second, and third trimesters showed a different trend. Conclusion: Accurate evaluation of patients, especially in the third trimester, is necessary from the point of view of increasing enzyme levels in other countries.

Using Second Measurement of De Ritis Ratio to Improve Mortality Prediction in Adult Trauma Patients in Intensive Care Unit.

The De Ritis ratio (DRR), the ratio of serum levels of aspartate aminotransferase/alanine aminotransferase, has been reported to be a valuable biomarker in risk stratification for many liver and non-liver diseases. This study aimed to explore whether the inclusion of DRR at the date of intensive care unit (ICU) admission or days after ICU admission improves the predictive performance of various prognosis prediction models. This study reviewed 888 adult trauma patients (74 deaths and 814 survivors) in the trauma registered database between 1 January 2009, and 31 December 2020. Medical information with AST and ALT levels and derived DRR at the date of ICU admission (1st DRR) and 3-7 day after ICU admission (2nd DRR) was retrieved. Logistic regression was used to build new probability models for mortality prediction using additional DRR variables in various mortality prediction models. There was no significant difference in the 1st DRR between the death and survival patients; however, there was a significantly higher 2nd DRR in the death patients than the survival patients. This study showed that the inclusion of the additional DRR variable, measured 3-7 days after ICU admission, significantly increased the prediction performance in all studied prognosis prediction models.

Liver enzyme delayed clearance in rat treated by CSF1 receptor specific antagonist Sotuletinib.

Sotuletinib (BLZ945), a CSF1-R specific kinase inhibitor developed for the treatment of Amyotrophic Lateral Sclerosis, induced liver enzyme elevation in absence of hepatocellular lesions in preclinical rat and monkey studies. The monocytic cell family, including Kupffer cells, e.g., the liver-resident macrophages, are dependent upon CSF1 pathway activation for their survival, proliferation, and differentiation. Kupffer cells act as the main body compartment responsible for elimination of some blood-borne proteins, like ALT, AST, and few others. The depletion of Kupffer cells through CSF1 pathway inhibition has already been hypothesized as responsible for apparent liver enzyme elevation without detectable corresponding liver damage. However, a release of these biomarkers from unseen hepatic lesions or from other organs cannot be excluded. In order to eliminate a potential contribution of ALT elevation from an internal organ source, we injected recombinant his-Tagged ALT1 into rats pretreated with Sotuletinib. The elimination rate of the exogenous ALT1 was significantly lower in treated animals, demonstrating a delayed clearance independently of any potential organ lesions.

Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone.

Objective: In clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the "grey zone (GZ)". This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients. Methods: Patients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver. Results: A total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = -13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = -0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients <30 years old were 32.4% and 35.8%, respectively, while the ratio of EHI increased to 43.2% once patients were older than 30 years but still in the IT and IHC stages. Conclusion: Setting 30 years old as a cut-off and lowering the ALT threshold could facilitate screening for the presence of significant liver injury, especially for GZ patients. IL-6 was a good indicator of EHI, and MCP-1 was significantly positively correlated with HBV DNA but negatively correlated with liver fibrosis.

Association between Elevated De Ritis Ratio and Mortality Outcome in Adult Patients with Thoracoabdominal Trauma.

The De Ritis ratio is widely used to differentiate various causes of liver disease and serves as an independent prognostic predictor for different malignancies and non-malignant illnesses. This retrospective study aimed to identify the association between the De Ritis ratio on admission and mortality outcomes in adult thoracoabdominal trauma patients. A total of 2248 hospitalized adult trauma patients with thoracoabdominal injury, defined as an abbreviated injury scale (AIS) score ≥ 1 in the thoracic and abdominal regions, between 1 January 2009, and 31 December 2019, were included. They were categorized into three tertile groups according to the De Ritis ratio. A 1:1 propensity score-matched study group was established to attenuate the confounding effect of patient characteristics on the mortality outcome assessment. The AST levels of the tertile 1, 2, and 3 groups were 115.8 ± 174.9, 115.7 ± 262.0, and 140.5 ± 209.7 U/L, respectively. Patients in the tertile 3 group had a significantly higher level of AST than those in the tertile 1 group (p = 0.032). In addition, patients in the tertile 1 group had a significantly higher level of ALT than those in the tertile 2 and 3 groups (115.9 ± 158.1 U/L vs. 74.5 ± 107.0 U/L and 61.9 ± 86.0 U/L, p < 0.001). The increased De Ritis ratio in trauma patients with thoracoabdominal injuries was mainly attributed to elevated AST levels. The propensity score-matched patient cohorts revealed that the patients in the tertile 3 group presented a 3.89-fold higher risk of mortality than the patients in the tertile 2 group. In contrast, the patients in the tertile 1 group did not have a significantly different mortality rate than those in the tertile 2 group. This study suggests that a De Ritis ratio > 1.64 may be a useful biomarker to identify patients with a higher risk for mortality.

Sofosbuvir in the Treatment of Hepatitis E virus Infection: A Review of in vitro and in vivo Evidence.

Chronic hepatitis E virus (HEV) infection, which occurs almost exclusively in immunocompromised patients, if untreated may progress to cirrhosis and possibly hepatocellular carcinoma. The reduction of immunosuppression and/or administration of ribavirin is frequently curative but there remain many immunocompromised individuals whose HEV infection is refractory to these therapeutic strategies. Moreover, the haematological toxicity of ribavirin limits its use. Pegylated interferon has demonstrated success in a small number of patients with chronic HEV infection; however, the potentially increased risk of graft rejection associated with its use renders it unsuitable for many transplant recipients. Alternative therapeutic strategies are therefore required. This article reviews the in vitro and in vivo literature to date of the antiviral agent sofosbuvir (well established in the treatment of hepatitis C) in the treatment of HEV infection.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

Background: Polyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury. Methods: This study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated. Results: The final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: -3.7, 95% CI, -6.0 to -1.5 U/L/day; -2.4, 95% CI, -4.5 to -0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (-5.2, 95% CI, -5.8 to -4.5 U/L/day; -3.5, 95% CI, -4.2 to -2.7 U/L/day; -4.9, 95% CI, -6.2 to -3.7 U/L/day, -0.07, 95% CI, -0.09 to -0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (-2.6, 95% CI, -3.3 to -1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (-1.4, 95% CI, -2.4 to -0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC. Conclusion: This was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.